Copyright © 2014 by the American Thoracic Society. Hypoxemia is a major complication of chronic obstructive pulmonary disease (COPD) that correlateswith disease prognosis. Identifying genetic variants associated with oxygenation may provide clues for deciphering the heterogeneity in prognosis among patients with COPD. However, previous genetic studies have been restricted to investigating COPD candidate genes for associationwith hypoxemia.Toreport results fromthe first genome-wide association study (GWAS) of resting oxygen saturation (as measured by pulse oximetry [SpO2]) in subjects with COPD, we performed a GWAS of SpO2 in two large, well characterized COPD populations:COPDGene, including both thenon-Hispanicwhite(NHW) and African American (AA) groups, and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE).We identified several suggestive loci (P < 1 × 1025) associated with SpO2 in COPDGenein theNHW(n=2810) andECLIPSE (n=1758)groups,and two loci on chromosomes 14 and 15 in the AA group (n = 820) from COPDGene achieving a level of genome-wide significance (P < 5 × 10-8). The chromosome 14 single-nucleotide polymorphism, rs6576132, located in an intergenic region, was nominally replicated (P<0.05) in the NHW group from COPDGene. The chromosome 15 single-nucleotide polymorphisms were rare in subjects of European ancestry, so the results couldnot be replicated.The chromosome15 region contains several genes, including TICRR and KIF7, and is proximal to RHCG (Rh family C glyocoprotein gene).We have identified two loci associated with resting oxygen saturation in AA subjects with COPD, and several suggestive regions in subjects of European descentwith COPD.Our study highlights the importance of investigating the genetics of complex traits in different racial groups.